5-75653218-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001276713.2(ANKDD1B):c.875T>C(p.Val292Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00825 in 1,535,996 control chromosomes in the GnomAD database, including 687 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (348 hom., cov: 33)
  • Exomes 𝑓: 0.0049 (339 hom.)
• Consequence: ANKDD1B NM_001276713.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.662

Genes affected

ANKDD1B (HGNC:32525): (ankyrin repeat and death domain containing 1B) Predicted to be involved in signal transduction. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014633238).
• BP6: Variant 5-75653218-T-C is Benign according to our data. Variant chr5-75653218-T-C is described in ClinVar as [Benign]. Clinvar id is 792001.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKDD1B	NM_001276713.2	c.875T>C	p.Val292Ala	missense_variant	8/14	ENST00000601380.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKDD1B	ENST00000601380.4	c.875T>C	p.Val292Ala	missense_variant	8/14	5	NM_001276713.2	P1

Frequencies

GnomAD3 genomes AF: 0.0391 AC: 5957 AN: 152162 Hom.: 350 Cov.: 33

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0220

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0281

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.0340

GnomAD3 exomes AF: 0.0112 AC: 1532 AN: 137058 Hom.: 72 AF XY: 0.00900 AC XY: 671 AN XY: 74524

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.0101

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0287

Gnomad SAS exome AF: 0.000934

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00108

Gnomad OTH exome AF: 0.00929

GnomAD4 exome AF: 0.00486 AC: 6724 AN: 1383716 Hom.: 339 Cov.: 30 AF XY: 0.00438 AC XY: 2992 AN XY: 682796

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.0117

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0198

Gnomad4 SAS exome AF: 0.00103

Gnomad4 FIN exome AF: 0.0000295

Gnomad4 NFE exome AF: 0.000455

Gnomad4 OTH exome AF: 0.0122

GnomAD4 genome AF: 0.0391 AC: 5954 AN: 152280 Hom.: 348 Cov.: 33 AF XY: 0.0369 AC XY: 2745 AN XY: 74468

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0220

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0282

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000735

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.0166 Hom.: 75

Bravo AF: 0.0453

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ExAC AF: 0.00726 AC: 136

Asia WGS AF: 0.0180 AC: 61 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	2.2
Dann	Benign	0.60
DEOGEN2	Benign	0.00097	T
FATHMM_MKL	Benign	0.088	N
LIST_S2	Benign	0.36	T
MetaRNN	Benign	0.0015	T
MutationAssessor	Benign	-0.23	N
PrimateAI	Benign	0.30	T
Sift4G	Benign	0.58	T
Vest4		0.067
GERP RS		2.9
Varity_R		0.028
gMVP		0.33

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

LitVar

Other links and lift over

dbSNP: rs10942740; hg19: chr5-74949043;