rs1434598021

Variant names:

• chr5-110420605-A-G
• rs1434598021
• NM_001039763.4:c.1949T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-110420605-A-G
• chr5-110420605-A-T

Variant summary

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

The NM_001039763.4(TMEM232):​c.1949T>C​(p.Leu650Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000752 in 1,328,950 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L650H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: TMEM232 NM_001039763.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.13
• Publications: 0 publications found

Genes affected

TMEM232 (HGNC:37270): (transmembrane protein 232) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039763.4. 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
	TMEM232	NM_001039763.4	MANE Select	c.1949T>C	p.Leu650Pro	missense	Exon 14 of 14	NP_001034852.3	C9JQI7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM232	ENST00000455884.7	TSL:2 MANE Select	c.1949T>C	p.Leu650Pro	missense	Exon 14 of 14	ENSP00000401477.2	C9JQI7-1
	TMEM232	ENST00000512003.7	TSL:1	n.*1243T>C		non_coding_transcript_exon	Exon 11 of 11	ENSP00000427785.2	E5RG73
	TMEM232	ENST00000515518.6	TSL:1	n.1621T>C		non_coding_transcript_exon	Exon 12 of 13

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.52e-7 AC: 1 AN: 1328950 Hom.: 0 Cov.: 30 AF XY: 0.00000153 AC XY: 1 AN XY: 654804

African (AFR) AF: 0.00 AC: 0 AN: 27274

American (AMR) AF: 0.00 AC: 0 AN: 20726

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23442

East Asian (EAS) AF: 0.00 AC: 0 AN: 32826

South Asian (SAS) AF: 0.00 AC: 0 AN: 68372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33430

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5464

European-Non Finnish (NFE) AF: 9.42e-7 AC: 1 AN: 1061936

Other (OTH) AF: 0.00 AC: 0 AN: 55480

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.81	L
PhyloP100		4.1
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.21
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.72
MutPred		0.20		Gain of glycosylation at L650 (P = 0.0071)
MVP		0.19
ClinPred		0.88	D
GERP RS		4.4
Varity_R		0.43
gMVP		0.075
Mutation Taster		=46/54	disease causing

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: rs1434598021; hg19: chr5-109756306;