1-145872691-A-C

Position:

• chr1-145872691-A-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_144698.5(ANKRD35):​c.2078T>G​(p.Leu693Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ANKRD35 NM_144698.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0710

Genes affected

ANKRD35 (HGNC:26323): (ankyrin repeat domain 35)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051315367).
• BP6: Variant 1-145872691-A-C is Benign according to our data. Variant chr1-145872691-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2285272.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD35	NM_144698.5	c.2078T>G	p.Leu693Arg	missense_variant	10/14	ENST00000355594.9	NP_653299.4
ANKRD35	NM_001280799.2	c.1808T>G	p.Leu603Arg	missense_variant	8/12		NP_001267728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD35	ENST00000355594.9	c.2078T>G	p.Leu693Arg	missense_variant	10/14	2	NM_144698.5	ENSP00000347802.4
ANKRD35	ENST00000544626.2	c.1808T>G	p.Leu603Arg	missense_variant	8/12	5		ENSP00000442671.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 96

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.033
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.3
DANN	Benign	0.90
DEOGEN2	Benign	0.0081	.;T
LIST_S2	Benign	0.56	.;T
MetaRNN	Benign	0.051	T;T
PROVEAN	Benign	1.7	N;.
Sift	Benign	1.0	T;.
Sift4G	Benign	1.0	T;T
Vest4		0.086
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-145562390;