7-118236893-C-A

Position:

• chr7-118236893-C-A

Variant summary

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

The NM_019644.4(ANKRD7):​c.679C>A​(p.Leu227Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 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: ANKRD7 NM_019644.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.71

Genes affected

ANKRD7 (HGNC:18588): (ankyrin repeat domain 7) Predicted to act upstream of or within blastocyst hatching. Located in centrosome and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD7	NM_019644.4	c.679C>A	p.Leu227Met	missense_variant	5/7	ENST00000265224.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD7	ENST00000265224.9	c.679C>A	p.Leu227Met	missense_variant	5/7	1	NM_019644.4	P2
ANKRD7	ENST00000417525.5	c.679C>A	p.Leu227Met	missense_variant	5/7	5		A2
ANKRD7	ENST00000477532.5	c.163C>A	p.Leu55Met	missense_variant	5/6	5
ANKRD7	ENST00000433239.6	n.636C>A		non_coding_transcript_exon_variant	5/16	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.679C>A (p.L227M) alteration is located in exon 5 (coding exon 5) of the ANKRD7 gene. This alteration results from a C to A substitution at nucleotide position 679, causing the leucine (L) at amino acid position 227 to be replaced by a methionine (M). 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	0.13
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T;T;.
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.35	T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.48	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.5	.;L;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.35	.;N;.
REVEL	Benign	0.14
Sift	Benign	0.12	.;T;.
Sift4G	Benign	0.19	T;T;T
Polyphen		0.98	.;D;.
Vest4		0.53
MVP		0.39
MPC		0.39
ClinPred		0.50	D
GERP RS		4.3
Varity_R		0.078
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1179418341; hg19: chr7-117876947;