7-118236824-C-T

Variant names:

• chr7-118236824-C-T
• rs1809738407
• NM_019644.4:c.610C>T

Variant summary

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

The NM_019644.4(ANKRD7):​c.610C>T​(p.Pro204Ser) 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: ANKRD7 NM_019644.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.793

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061571836).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD7	NM_019644.4	c.610C>T	p.Pro204Ser	missense_variant	Exon 5 of 7	ENST00000265224.9	NP_062618.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD7	ENST00000265224.9	c.610C>T	p.Pro204Ser	missense_variant	Exon 5 of 7	1	NM_019644.4	ENSP00000265224.4
ANKRD7	ENST00000417525.5	c.610C>T	p.Pro204Ser	missense_variant	Exon 5 of 7	5		ENSP00000395595.2
ANKRD7	ENST00000477532.5	c.94C>T	p.Pro32Ser	missense_variant	Exon 5 of 6	5		ENSP00000489121.1
ANKRD7	ENST00000433239.6	n.567C>T		non_coding_transcript_exon_variant	Exon 5 of 16	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.610C>T (p.P204S) alteration is located in exon 5 (coding exon 5) of the ANKRD7 gene. This alteration results from a C to T substitution at nucleotide position 610, causing the proline (P) at amino acid position 204 to be replaced by a serine (S). 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	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.78
DANN	Benign	0.18
DEOGEN2	Benign	0.0057	T;T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.22	T;T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.062	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.42	.;N;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.64	.;N;.
REVEL	Benign	0.013
Sift	Benign	0.40	.;T;.
Sift4G	Benign	0.64	T;T;T
Polyphen		0.0	.;B;.
Vest4		0.14
MutPred		0.35		.;Loss of catalytic residue at P203 (P = 0.0151);Loss of catalytic residue at P203 (P = 0.0151);
MVP		0.072
MPC		0.27
ClinPred		0.046	T
GERP RS		-0.86
Varity_R		0.018
gMVP		0.34

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: rs1809738407; hg19: chr7-117876878; COSMIC: COSV54553966; COSMIC: COSV54553966;