NM_001195597.2:c.273A>T

Variant names:

• chr6-130834904-A-T
• rs1184742806
• NM_001195597.2:c.273A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195597.2(SMLR1):​c.273A>T​(p.Gln91His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000868 in 1,383,098 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: 0.0000087 (0 hom.)
• Consequence: SMLR1 NM_001195597.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0180
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12228286).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195597.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMLR1	NM_001195597.2	MANE Select	c.273A>T	p.Gln91His	missense	Exon 2 of 2	NP_001182526.1	H3BR10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMLR1	ENST00000541421.2	TSL:1 MANE Select	c.273A>T	p.Gln91His	missense	Exon 2 of 2	ENSP00000456026.1	H3BR10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000146 AC: 2 AN: 136536 AF XY: 0.0000135

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000365

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000868 AC: 12 AN: 1383098 Hom.: 0 Cov.: 30 AF XY: 0.00000586 AC XY: 4 AN XY: 682506

African (AFR) AF: 0.00 AC: 0 AN: 31534

American (AMR) AF: 0.00 AC: 0 AN: 35686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25150

East Asian (EAS) AF: 0.00 AC: 0 AN: 35728

South Asian (SAS) AF: 0.00 AC: 0 AN: 79208

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.0000102 AC: 11 AN: 1078360

Other (OTH) AF: 0.0000173 AC: 1 AN: 57858

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	9.9
DANN	Benign	0.81
DEOGEN2	Benign	0.055	T
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.12	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.018
PrimateAI	Benign	0.23	T
PROVEAN	Uncertain	-3.5	D
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.019	D
Vest4		0.093
MVP		0.055
GERP RS		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.15
gMVP		0.048
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs1184742806; hg19: chr6-131156044;