6-34246545-C-T

Variant names:

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

Variant summary

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

The ENST00000636500.1(SMIM29):​c.449G>A​(p.Gly150Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/16 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: not found (cov: 35)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: 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=0.057890743).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000636500.1. 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
	SMIM29	NM_001008703.4	MANE Select	c.*258G>A		3_prime_UTR	Exon 5 of 5	NP_001008703.2	Q86T20-1
	SMIM29	NM_178508.6		c.*258G>A		3_prime_UTR	Exon 5 of 5	NP_848603.3	Q86T20-1
	SMIM29	NM_001008704.4		c.*258G>A		3_prime_UTR	Exon 5 of 5	NP_001008704.2	Q86T20-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SMIM29	ENST00000636500.1	TSL:1	c.449G>A	p.Gly150Glu	missense	Exon 5 of 5	ENSP00000489784.1	A0A2U3TZT1
	SMIM29	ENST00000476320.6	TSL:2 MANE Select	c.*258G>A		3_prime_UTR	Exon 5 of 5	ENSP00000417604.2	Q86T20-1
	SMIM29	ENST00000481533.5	TSL:1	c.*258G>A		3_prime_UTR	Exon 5 of 5	ENSP00000418062.2	Q86T20-1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1416802 Hom.: 0 Cov.: 59 AF XY: 0.00 AC XY: 0 AN XY: 698574

African (AFR) AF: 0.00 AC: 0 AN: 32396

American (AMR) AF: 0.00 AC: 0 AN: 40490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23268

East Asian (EAS) AF: 0.00 AC: 0 AN: 39108

South Asian (SAS) AF: 0.00 AC: 0 AN: 80542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5504

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085892

Other (OTH) AF: 0.00 AC: 0 AN: 58296

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	2.1
DANN	Benign	0.86
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.28
MutPred		0.24		Gain of helix (P = 0.027)
ClinPred		0.092	T
GERP RS		0.41
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.099
Mutation Taster		=100/0	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: rs1150781; hg19: chr6-34214322;