chr1-145960777-C-T

Variant names:

• chr1-145960777-C-T
• rs145762629
• NM_001039888.4:c.983G>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001039888.4(ANKRD34A):​c.983G>A​(p.Gly328Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: ANKRD34A NM_001039888.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.970

Genes affected

ANKRD34A (HGNC:27639): (ankyrin repeat domain 34A)

ENSG00000280778 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17770973).
• BS2: High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD34A	NM_001039888.4	c.983G>A	p.Gly328Glu	missense_variant	Exon 4 of 4	ENST00000606888.3	NP_001034977.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD34A	ENST00000606888.3	c.983G>A	p.Gly328Glu	missense_variant	Exon 4 of 4	2	NM_001039888.4	ENSP00000475189.1
ENSG00000280778	ENST00000625258.1	c.-29-16307C>T		intron_variant	Intron 1 of 3	5		ENSP00000487094.1
ENSG00000280778	ENST00000630636.1	n.713+1673C>T		intron_variant	Intron 3 of 5	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251300 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135860

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461890 Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000135

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.983G>A (p.G328E) alteration is located in exon 4 (coding exon 1) of the ANKRD34A gene. This alteration results from a G to A substitution at nucleotide position 983, causing the glycine (G) at amino acid position 328 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Benign	0.91
DEOGEN2	Benign	0.024	T
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.18	T
Sift4G	Benign	0.46	T
Vest4		0.29
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs145762629; hg19: chr1-145474311;