chr7-99610253-T-A

Variant names:

• chr7-99610253-T-A
• rs7792939
• NM_001195541.3:c.494-140T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001195541.3(TMEM225B):​c.494-140T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000252 in 594,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: TMEM225B NM_001195541.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.206
• Publications: 25 publications found

Genes affected

TMEM225B (HGNC:53075): (transmembrane protein 225B) Predicted to be involved in negative regulation of phosphatase activity. 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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMEM225B	NM_001195541.3	c.494-140T>A		intron_variant	Intron 5 of 5	ENST00000431679.6	NP_001182470.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMEM225B	ENST00000431679.6	c.494-140T>A		intron_variant	Intron 5 of 5	5	NM_001195541.3	ENSP00000492416.1
TMEM225B	ENST00000453227.5	c.494-140T>A		intron_variant	Intron 5 of 5	5		ENSP00000491691.1

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000113 AC: 5 AN: 442070 Hom.: 0 AF XY: 0.0000130 AC XY: 3 AN XY: 230198

African (AFR) AF: 0.00 AC: 0 AN: 12634

American (AMR) AF: 0.000214 AC: 4 AN: 18656

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12992

East Asian (EAS) AF: 0.00 AC: 0 AN: 31000

South Asian (SAS) AF: 0.00 AC: 0 AN: 36760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27912

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1912

European-Non Finnish (NFE) AF: 0.00000364 AC: 1 AN: 274784

Other (OTH) AF: 0.00 AC: 0 AN: 25420

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74344

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.000458 AC: 7 AN: 15290

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 2915

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.0
DANN	Benign	0.40
PhyloP100		0.21

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7792939; hg19: chr7-99207876;