16-21250432-A-T

Position:

• chr16-21250432-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145865.3(ANKS4B):​c.866A>T​(p.Asp289Val) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ANKS4B NM_145865.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0780

Genes affected

ANKS4B (HGNC:26795): (ankyrin repeat and sterile alpha motif domain containing 4B) Involved in brush border assembly; cellular protein-containing complex assembly; and protein localization to microvillus. Located in brush border and microvillus. [provided by Alliance of Genome Resources, Apr 2022]

CRYM (HGNC:2418): (crystallin mu) Crystallins are separated into two classes: taxon-specific and ubiquitous. The former class is also called phylogenetically-restricted crystallins. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. This gene encodes a taxon-specific crystallin protein that binds NADPH and has sequence similarity to bacterial ornithine cyclodeaminases. The encoded protein does not perform a structural role in lens tissue, and instead it binds thyroid hormone for possible regulatory or developmental roles. Mutations in this gene have been associated with autosomal dominant non-syndromic deafness. [provided by RefSeq, Sep 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.072418064).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKS4B	NM_145865.3	c.866A>T	p.Asp289Val	missense_variant	2/2	ENST00000311620.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKS4B	ENST00000311620.7	c.866A>T	p.Asp289Val	missense_variant	2/2	1	NM_145865.3	P1
CRYM	ENST00000574448.5	c.*521-6364T>A		intron_variant, NMD_transcript_variant		1
CRYM	ENST00000570401.5	c.265-6364T>A		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center

Jul 25, 2023

Gene of Uncertain Significance -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	13
DANN	Benign	0.92
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.12	N
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
MutationTaster	Benign	0.96	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.096
Sift	Benign	0.28	T
Sift4G	Benign	0.29	T
Polyphen		0.11	B
Vest4		0.17
MutPred		0.31		Gain of MoRF binding (P = 0.0994);
MVP		0.57
MPC		0.36
ClinPred		0.12	T
GERP RS		3.4
Varity_R		0.14
gMVP		0.16

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: chr16-21261753;