rs1569727603

Variant names:

• chr1-34985211-A-G
• rs1569727603
• NM_001195156.2:c.95T>C

Variant summary

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

The NM_001195156.2(TMEM35B):​c.95T>C​(p.Val32Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000866 in 1,385,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000087 (0 hom.)
• Consequence: TMEM35B NM_001195156.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.129
• Publications: 0 publications found

Genes affected

TMEM35B (HGNC:40021): (transmembrane protein 35B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000284773 (HGNC:):

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=0.07157585).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195156.2. 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
	TMEM35B	NM_001195156.2	MANE Select	c.95T>C	p.Val32Ala	missense	Exon 1 of 3	NP_001182085.1	Q8NCS4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM35B	ENST00000373337.4	TSL:1 MANE Select	c.95T>C	p.Val32Ala	missense	Exon 1 of 3	ENSP00000362435.3	Q8NCS4
	ENSG00000284773	ENST00000417456.1	TSL:2	c.95T>C	p.Val32Ala	missense	Exon 1 of 2	ENSP00000493999.1	A0A2R8YCV2
	ENSG00000271741	ENST00000487874.1	TSL:5	n.2147-1264T>C		intron	N/A	ENSP00000421752.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000866 AC: 12 AN: 1385870 Hom.: 0 Cov.: 31 AF XY: 0.00000878 AC XY: 6 AN XY: 683584

African (AFR) AF: 0.00 AC: 0 AN: 29834

American (AMR) AF: 0.00 AC: 0 AN: 34930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24736

East Asian (EAS) AF: 0.00 AC: 0 AN: 34062

South Asian (SAS) AF: 0.00 AC: 0 AN: 78256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5630

European-Non Finnish (NFE) AF: 0.0000102 AC: 11 AN: 1074308

Other (OTH) AF: 0.0000174 AC: 1 AN: 57512

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.094
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.5
DANN	Benign	0.65
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.13
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.023
Sift	Benign	0.33	T
Sift4G	Benign	0.20	T
Polyphen		0.0060	B
Vest4		0.039
MutPred		0.35		Gain of disorder (P = 0.0283)
MVP		0.014
ClinPred		0.063	T
GERP RS		-1.3
PromoterAI		-0.093	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.041
gMVP		0.59
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1569727603; hg19: chr1-35450812;