7-129512341-T-C

Variant names:

• chr7-129512341-T-C
• rs1449867805
• NM_001195243.2:c.98T>C

Variant summary

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

The NM_001195243.2(SMKR1):​c.98T>C​(p.Leu33Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,383,776 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: SMKR1 NM_001195243.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.39

Genes affected

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

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
SMKR1	NM_001195243.2	c.98T>C	p.Leu33Pro	missense_variant	Exon 2 of 2	ENST00000462322.3	NP_001182172.1
SMKR1	XM_024446620.2	c.155T>C	p.Leu52Pro	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.98T>C	p.Leu33Pro	missense_variant	Exon 2 of 2	1	NM_001195243.2	ENSP00000454370.1
SMKR1	ENST00000488846.1	n.127T>C		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000434 AC: 6 AN: 1383776 Hom.: 0 Cov.: 30 AF XY: 0.00000439 AC XY: 3 AN XY: 682832

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: 0.0000126

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000463

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.98T>C (p.L33P) alteration is located in exon 2 (coding exon 2) of the SMKR1 gene. This alteration results from a T to C substitution at nucleotide position 98, causing the leucine (L) at amino acid position 33 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	Pathogenic	0.79
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Benign	22
DANN	Benign	0.83
DEOGEN2	Benign	0.13	T
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.090	D
MetaRNN	Uncertain	0.67	D
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-2.5	N
Sift	Benign	0.11	T
Sift4G	Benign	0.23	T
Vest4		0.74
MVP		0.64
GERP RS		5.7
Varity_R		0.62
gMVP		0.61

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: rs1449867805; hg19: chr7-129152182;