6-130834931-GT-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001195597.2(SMLR1):c.301del(p.Tyr101ThrfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,535,314 control chromosomes in the GnomAD database, including 15 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (13 hom.)
• Consequence: SMLR1 NM_001195597.2 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.10

Genes affected

SMLR1 (HGNC:44670): (small leucine rich protein 1) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 6-130834931-GT-G is Benign according to our data. Variant chr6-130834931-GT-G is described in ClinVar as [Likely_benign]. Clinvar id is 2656910.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMLR1	NM_001195597.2	c.301del	p.Tyr101ThrfsTer4	frameshift_variant	2/2	ENST00000541421.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMLR1	ENST00000541421.2	c.301del	p.Tyr101ThrfsTer4	frameshift_variant	2/2	1	NM_001195597.2	P1

Frequencies

GnomAD3 genomes AF: 0.00237 AC: 361 AN: 152152 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.00791

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00345

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00212 AC: 290 AN: 136572 Hom.: 1 AF XY: 0.00213 AC XY: 158 AN XY: 74146

Gnomad AFR exome AF: 0.000778

Gnomad AMR exome AF: 0.000613

Gnomad ASJ exome AF: 0.000241

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00280

Gnomad FIN exome AF: 0.00818

Gnomad NFE exome AF: 0.00281

Gnomad OTH exome AF: 0.00169

GnomAD4 exome AF: 0.00277 AC: 3834 AN: 1383044 Hom.: 13 Cov.: 30 AF XY: 0.00284 AC XY: 1935 AN XY: 682474

Gnomad4 AFR exome AF: 0.000190

Gnomad4 AMR exome AF: 0.000504

Gnomad4 ASJ exome AF: 0.0000795

Gnomad4 EAS exome AF: 0.0000280

Gnomad4 SAS exome AF: 0.00317

Gnomad4 FIN exome AF: 0.00788

Gnomad4 NFE exome AF: 0.00293

Gnomad4 OTH exome AF: 0.00223

GnomAD4 genome AF: 0.00237 AC: 361 AN: 152270 Hom.: 2 Cov.: 32 AF XY: 0.00261 AC XY: 194 AN XY: 74444

Gnomad4 AFR AF: 0.000409

Gnomad4 AMR AF: 0.000589

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.00791

Gnomad4 NFE AF: 0.00344

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00298 Hom.: 0

Bravo AF: 0.00163

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

SMLR1: BS2 -

Computational scores

Source: dbNSFP v4.3

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: rs765201462; hg19: chr6-131156071; COSMIC: COSV104397304; COSMIC: COSV104397304;