rs1295480130

Variant names:

• chr19-3474985-C-G
• rs1295480130
• NM_001136503.2:c.251G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-3474985-C-G
• chr19-3474985-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001136503.2(SMIM24):​c.251G>C​(p.Arg84Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R84K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SMIM24 NM_001136503.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.882
• Publications: 0 publications found

Genes affected

SMIM24 (HGNC:37244): (small integral membrane protein 24) Predicted to be located in membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04572013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMIM24	NM_001136503.2	c.251G>C	p.Arg84Thr	missense_variant	Exon 4 of 4	ENST00000215531.6	NP_001129975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMIM24	ENST00000215531.6	c.251G>C	p.Arg84Thr	missense_variant	Exon 4 of 4	1	NM_001136503.2	ENSP00000215531.4
SMIM24	ENST00000587847.1	c.41G>C	p.Arg14Thr	missense_variant	Exon 3 of 3	1		ENSP00000465692.1
SMIM24	ENST00000591708.1	c.41G>C	p.Arg14Thr	missense_variant	Exon 2 of 2	2		ENSP00000467484.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399116 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 690058

African (AFR) AF: 0.00 AC: 0 AN: 31572

American (AMR) AF: 0.00 AC: 0 AN: 35688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49056

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078940

Other (OTH) AF: 0.00 AC: 0 AN: 58010

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.22
DANN	Benign	0.42
DEOGEN2	Benign	0.0080	T;.;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.41	T;.;T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.046	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.;.
PhyloP100		-0.88
PROVEAN	Benign	-0.97	N;.;.
REVEL	Benign	0.011
Sift	Benign	0.077	T;.;.
Sift4G	Benign	0.47	T;T;T
Polyphen		0.089	B;.;.
Vest4		0.11
MutPred		0.16		Gain of phosphorylation at R84 (P = 0.0031);.;.;
MVP		0.014
ClinPred		0.030	T
GERP RS		-2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.066
gMVP		0.012
Mutation Taster		=94/6	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: rs1295480130; hg19: chr19-3474983;