6-34246762-C-G

Variant names:

• chr6-34246762-C-G
• rs202129859
• ENST00000636500.1:c.232G>C

Variant summary

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

The ENST00000636500.1(SMIM29):​c.232G>C​(p.Asp78His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,130 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D78Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SMIM29 ENST00000636500.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.276
• Publications: 0 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: 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=0.102867305).

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.*41G>C		3_prime_UTR	Exon 5 of 5	NP_001008703.2	Q86T20-1
	SMIM29	NM_178508.6		c.*41G>C		3_prime_UTR	Exon 5 of 5	NP_848603.3	Q86T20-1
	SMIM29	NM_001008704.4		c.*41G>C		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.232G>C	p.Asp78His	missense	Exon 5 of 5	ENSP00000489784.1	A0A2U3TZT1
	SMIM29	ENST00000476320.6	TSL:2 MANE Select	c.*41G>C		3_prime_UTR	Exon 5 of 5	ENSP00000417604.2	Q86T20-1
	SMIM29	ENST00000481533.5	TSL:1	c.*41G>C		3_prime_UTR	Exon 5 of 5	ENSP00000418062.2	Q86T20-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461130 Hom.: 0 Cov.: 62 AF XY: 0.00 AC XY: 0 AN XY: 726842

African (AFR) AF: 0.00 AC: 0 AN: 33474

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52824

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111936

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.1
DANN	Benign	0.79
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.28
MutPred		0.28		Gain of sheet (P = 0.0101)
ClinPred		0.33	T
GERP RS		-0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.030
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: rs202129859; hg19: chr6-34214539;