ANK1 p.Val1755Val

Variant names:

• chr8-41668396-C-A
• NM_000037.4:c.5265G>T
• ANK1 p.Val1755Val

Your query was ambiguous. Multiple possible variants found:

• chr8-41668396-C-A
• chr8-41668396-C-G
• chr8-41668396-C-T

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-2 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_ModerateB4_Strong

The NM_000037.4(ANK1):c.5265G>T (p.Val1755Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (REVEL) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANK1 NM_000037.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 0 publications found

Genes affected

ANK1 (HGNC:492): (ankyrin 1) Ankyrins are a family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton and play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. Multiple isoforms of ankyrin with different affinities for various target proteins are expressed in a tissue-specific, developmentally regulated manner. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. Ankyrin 1, the prototype of this family, was first discovered in the erythrocytes, but since has also been found in brain and muscles. Mutations in erythrocytic ankyrin 1 have been associated in approximately half of all patients with hereditary spherocytosis. Complex patterns of alternative splicing in the regulatory domain, giving rise to different isoforms of ankyrin 1 have been described. Truncated muscle-specific isoforms of ankyrin 1 resulting from usage of an alternate promoter have also been identified. [provided by RefSeq, Dec 2008]

ANK1 Gene-Disease associations (from GenCC):

• hereditary spherocytosis

  Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen
• hereditary spherocytosis type 1

  Inheritance: SD, AR, AD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -2 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])
	B4Synonymous/intronic, no splicing impact		Synonymous/intronic variant with confirmed no splicing impact (B4 strong); Synonymous variant — splicing algorithms confirm no impact on splicing (B4 strong [-4])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000037.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ANK1 NM_000037.4	MANE Select	c.5265G>T p.Val1755Val	synonymous	Exon 39 of 43	Prot: NP_000028.3
	ANK1 NM_001142446.2		c.5388G>T p.Val1796Val	synonymous	Exon 40 of 43	Prot: NP_001135918.1 UniProt:
	ANK1 NM_020476.3		c.5265G>T p.Val1755Val	synonymous	Exon 39 of 42	Prot: NP_065209.2 UniProt:

ANK1 NM_000037.4

MANE Select

HGVSc / HGVSpc.5265G>Tp.Val1755Val

Exon rankExon 39 of 43

synonymous

Prot: NP_000028.3

ANK1 NM_001142446.2

HGVSc / HGVSpc.5388G>Tp.Val1796Val

Exon rankExon 40 of 43

synonymous

Prot: NP_001135918.1UniProt: P16157-21

ANK1 NM_020476.3

HGVSc / HGVSpc.5265G>Tp.Val1755Val

Exon rankExon 39 of 42

synonymous

Prot: NP_065209.2UniProt: P16157-1

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ANK1 ENST00000289734.13	TSL:1MANE Select	c.5265G>T p.Val1755Val	synonymous	Exon 39 of 43	Prot: ENSP00000289734.8 UniProt:
	ANK1 ENST00000265709.14	TSL:1	c.5388G>T p.Val1796Val	synonymous	Exon 40 of 43	Prot: ENSP00000265709.8 UniProt:
	ANK1 ENST00000347528.8	TSL:1	c.5265G>T p.Val1755Val	synonymous	Exon 39 of 42	Prot: ENSP00000339620.4 UniProt:

ANK1 ENST00000289734.13

TSL:1MANE Select

HGVSc / HGVSpc.5265G>Tp.Val1755Val

Exon rankExon 39 of 43

synonymous

Prot: ENSP00000289734.8UniProt: P16157-3

ANK1 ENST00000265709.14

TSL:1

HGVSc / HGVSpc.5388G>Tp.Val1796Val

Exon rankExon 40 of 43

synonymous

Prot: ENSP00000265709.8UniProt: P16157-21

ANK1 ENST00000347528.8

TSL:1

HGVSc / HGVSpc.5265G>Tp.Val1755Val

Exon rankExon 39 of 42

synonymous

Prot: ENSP00000339620.4UniProt: P16157-1

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 3 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:33
GnomAD4 exome	AF:	AC:	Hom:	AN:	Cov:37
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:33

Showing 3 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	9.1
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.6
DANN	Benign	0.64
GPN-Star LLR	N/A	-3.3
GPN-Star score	N/A	3.3
PhyloP100	Benign	1.3

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.010
SpliceAI score (max)	Benign	0.010	Details are displayed if max score is > 0.2

Showing 2 of 2 scores

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

hg19: chr8-41525914;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar