SMIM29 p.Ala151Val

Variant names:

• chr6-34246542-G-A
• rs532743703
• ENST00000636500.1:c.452C>T
• SMIM29 p.Ala151Val

Your query was ambiguous. Multiple possible variants found:

• chr6-34246542-G-A
• chr6-34246541-CG-AA
• chr6-34246541-CG-GA
• chr6-34246541-CG-TA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000636500.1(SMIM29):​c.452C>T​(p.Ala151Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000574 in 1,567,464 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000057 (0 hom.)
• Consequence: SMIM29 ENST00000636500.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.09
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059053153).
• BP6: Variant 6-34246542-G-A is Benign according to our data. Variant chr6-34246542-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3166584.Status of the report is criteria_provided_single_submitter, 1 stars.

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.*261C>T		3_prime_UTR	Exon 5 of 5	NP_001008703.2	Q86T20-1
	SMIM29	NM_178508.6		c.*261C>T		3_prime_UTR	Exon 5 of 5	NP_848603.3	Q86T20-1
	SMIM29	NM_001008704.4		c.*261C>T		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.452C>T	p.Ala151Val	missense	Exon 5 of 5	ENSP00000489784.1	A0A2U3TZT1
	SMIM29	ENST00000476320.6	TSL:2 MANE Select	c.*261C>T		3_prime_UTR	Exon 5 of 5	ENSP00000417604.2	Q86T20-1
	SMIM29	ENST00000481533.5	TSL:1	c.*261C>T		3_prime_UTR	Exon 5 of 5	ENSP00000418062.2	Q86T20-1

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152232 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000409 AC: 9 AN: 220178 AF XY: 0.0000510

Gnomad AFR exome AF: 0.0000631

Gnomad AMR exome AF: 0.0000652

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000498

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000572 AC: 81 AN: 1415114 Hom.: 0 Cov.: 29 AF XY: 0.0000502 AC XY: 35 AN XY: 697622

African (AFR) AF: 0.0000309 AC: 1 AN: 32364

American (AMR) AF: 0.0000496 AC: 2 AN: 40350

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23048

East Asian (EAS) AF: 0.0000766 AC: 3 AN: 39154

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5494

European-Non Finnish (NFE) AF: 0.0000645 AC: 70 AN: 1085644

Other (OTH) AF: 0.0000687 AC: 4 AN: 58238

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152350 Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3 AN XY: 74500

African (AFR) AF: 0.0000241 AC: 1 AN: 41578

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000182 Hom.: 0

Bravo AF: 0.0000567

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.10
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.51
DANN	Benign	0.68
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.059	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.027
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs532743703;

hg19: chr6-34214319;

COSMIC: COSV108847768;

COSMIC: COSV108847768;