9-136405152-C-A

Variant names:

• chr9-136405152-C-A
• rs893444250
• NM_001039707.2:c.944G>T

Variant summary

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

The NM_001039707.2(ENTR1):​c.944G>T​(p.Ser315Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ENTR1 NM_001039707.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.80

Genes affected

ENTR1 (HGNC:10667): (endosome associated trafficking regulator 1) Involved in several processes, including endocytic recycling; positive regulation of cilium assembly; and positive regulation of protein localization to cilium. Located in endosome; microtubule organizing center; and midbody. Colocalizes with retromer complex. [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 rank	MANE	Protein	UniProt
ENTR1	NM_001039707.2	c.944G>T	p.Ser315Ile	missense_variant	Exon 7 of 10	ENST00000357365.8	NP_001034796.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENTR1	ENST00000357365.8	c.944G>T	p.Ser315Ile	missense_variant	Exon 7 of 10	5	NM_001039707.2	ENSP00000349929.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461674 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727122

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.944G>T (p.S315I) alteration is located in exon 7 (coding exon 7) of the SDCCAG3 gene. This alteration results from a G to T substitution at nucleotide position 944, causing the serine (S) at amino acid position 315 to be replaced by an isoleucine (I). 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	0.20
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.069	T;.;.
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.68	T;T;T
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.52	D;D;D
MetaSVM	Benign	-0.55	T
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.015	D;D;D
Sift4G	Uncertain	0.048	D;T;T
Polyphen		0.99	D;D;D
Vest4		0.43
MutPred		0.39		Loss of disorder (P = 0.0183);.;.;
MVP		0.81
MPC		0.018
ClinPred		0.78	D
GERP RS		3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.090
gMVP		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs893444250; hg19: chr9-139299604;