7-129512410-C-T

Variant names:

• chr7-129512410-C-T
• rs1223595707
• NM_001195243.2:c.167C>T

Variant summary

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

The NM_001195243.2(SMKR1):​c.167C>T​(p.Ala56Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000723 in 1,382,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 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)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: SMKR1 NM_001195243.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.61

Genes affected

SMKR1 (HGNC:43561): (small lysine rich protein 1)

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=0.10519478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMKR1	NM_001195243.2	c.167C>T	p.Ala56Val	missense_variant	Exon 2 of 2	ENST00000462322.3	NP_001182172.1
SMKR1	XM_024446620.2	c.224C>T	p.Ala75Val	missense_variant	Exon 2 of 2		XP_024302388.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMKR1	ENST00000462322.3	c.167C>T	p.Ala56Val	missense_variant	Exon 2 of 2	1	NM_001195243.2	ENSP00000454370.1
SMKR1	ENST00000488846.1	n.196C>T		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000599 AC: 8 AN: 133508 Hom.: 0 AF XY: 0.0000550 AC XY: 4 AN XY: 72770

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000332

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000723 AC: 10 AN: 1382920 Hom.: 0 Cov.: 30 AF XY: 0.00000733 AC XY: 5 AN XY: 682466

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000254

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: 0.0000173

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

Feb 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.167C>T (p.A56V) alteration is located in exon 2 (coding exon 2) of the SMKR1 gene. This alteration results from a C to T substitution at nucleotide position 167, causing the alanine (A) at amino acid position 56 to be replaced by a valine (V). 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	-0.24	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.15	T
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.11	T
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.3	D
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.14	T
Vest4		0.17
MVP		0.24
GERP RS		3.8
Varity_R		0.16
gMVP		0.14

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: rs1223595707; hg19: chr7-129152251;