6-34246545-C-G

Variant names:

• chr6-34246545-C-G
• rs1150781
• ENST00000636500.1:c.449G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000636500.1(SMIM29):​c.449G>C​(p.Gly150Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.884 in 1,568,936 control chromosomes in the GnomAD database, including 619,375 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.79 (49855 hom., cov: 35)
  • Exomes 𝑓: 0.89 (569520 hom.)
• Consequence: SMIM29 ENST00000636500.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277
• Publications: 52 publications found

Genes affected

SMIM29 (HGNC:1340): (small integral membrane protein 29) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1070456E-6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.918 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMIM29	NM_001008703.4	c.*258G>C		3_prime_UTR_variant	Exon 5 of 5	ENST00000476320.6	NP_001008703.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMIM29	ENST00000476320.6	c.*258G>C		3_prime_UTR_variant	Exon 5 of 5	2	NM_001008703.4	ENSP00000417604.2

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120647 AN: 152134 Hom.: 49852 Cov.: 35

Gnomad AFR AF: 0.552

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.718

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.865

Gnomad SAS AF: 0.941

Gnomad FIN AF: 0.952

Gnomad MID AF: 0.882

Gnomad NFE AF: 0.912

Gnomad OTH AF: 0.793

GnomAD2 exomes AF: 0.848 AC: 189362 AN: 223316 AF XY: 0.867

Gnomad AFR exome AF: 0.542

Gnomad AMR exome AF: 0.620

Gnomad ASJ exome AF: 0.850

Gnomad EAS exome AF: 0.880

Gnomad FIN exome AF: 0.949

Gnomad NFE exome AF: 0.915

Gnomad OTH exome AF: 0.869

GnomAD4 exome AF: 0.893 AC: 1265521 AN: 1416684 Hom.: 569520 Cov.: 59 AF XY: 0.897 AC XY: 626551 AN XY: 698504

African (AFR) AF: 0.549 AC: 17762 AN: 32382

American (AMR) AF: 0.633 AC: 25612 AN: 40458

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 19827 AN: 23260

East Asian (EAS) AF: 0.833 AC: 32570 AN: 39108

South Asian (SAS) AF: 0.941 AC: 75755 AN: 80538

European-Finnish (FIN) AF: 0.947 AC: 48580 AN: 51302

Middle Eastern (MID) AF: 0.875 AC: 4817 AN: 5504

European-Non Finnish (NFE) AF: 0.912 AC: 989793 AN: 1085844

Other (OTH) AF: 0.872 AC: 50805 AN: 58288

GnomAD4 genome AF: 0.793 AC: 120688 AN: 152252 Hom.: 49855 Cov.: 35 AF XY: 0.796 AC XY: 59286 AN XY: 74452

African (AFR) AF: 0.552 AC: 22921 AN: 41504

American (AMR) AF: 0.717 AC: 10962 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2919 AN: 3472

East Asian (EAS) AF: 0.865 AC: 4480 AN: 5178

South Asian (SAS) AF: 0.941 AC: 4548 AN: 4834

European-Finnish (FIN) AF: 0.952 AC: 10118 AN: 10626

Middle Eastern (MID) AF: 0.877 AC: 256 AN: 292

European-Non Finnish (NFE) AF: 0.912 AC: 62035 AN: 68026

Other (OTH) AF: 0.794 AC: 1680 AN: 2116

Alfa AF: 0.892 Hom.: 33132

Bravo AF: 0.759

TwinsUK AF: 0.913 AC: 3387

ALSPAC AF: 0.924 AC: 3563

ESP6500AA AF: 0.573 AC: 2526

ESP6500EA AF: 0.903 AC: 7763

ExAC AF: 0.854 AC: 103375

Asia WGS AF: 0.859 AC: 2989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.7
DANN	Benign	0.93
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.30	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.28
ClinPred		0.0037	T
GERP RS		0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.051
Mutation Taster		=100/0	polymorphism (auto)

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: rs1150781; hg19: chr6-34214322; COSMIC: COSV58988465; COSMIC: COSV58988465;