7-129512250-G-C

Position:

• chr7-129512250-G-C

Variant summary

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

The NM_001195243.2(SMKR1):​c.7G>C​(p.Ala3Pro) 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. 12/16 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)
• Consequence: SMKR1 NM_001195243.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.70

Genes affected

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

SMKR1 (HGNC:):

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=0.13648608).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMKR1	NM_001195243.2	c.7G>C	p.Ala3Pro	missense_variant	2/2	ENST00000462322.3	NP_001182172.1
SMKR1	XM_024446620.2	c.65-1G>C		splice_acceptor_variant, intron_variant			XP_024302388.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMKR1	ENST00000462322.3	c.7G>C	p.Ala3Pro	missense_variant	2/2	1	NM_001195243.2	ENSP00000454370.1
SMKR1	ENST00000488846.1	n.37-1G>C		splice_acceptor_variant, intron_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Jun 27, 2022

The c.7G>C (p.A3P) alteration is located in exon 2 (coding exon 2) of the SMKR1 gene. This alteration results from a G to C substitution at nucleotide position 7, causing the alanine (A) at amino acid position 3 to be replaced by a proline (P). 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	0.081
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	19
DANN	Benign	0.79
DEOGEN2	Benign	0.022	T
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.14	T
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.8	N
Sift	Benign	0.052	T
Sift4G	Benign	0.12	T
Vest4		0.11
MVP		0.35
GERP RS		3.8
Varity_R		0.20
gMVP		0.094

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: chr7-129152091;