9-68537489-C-T

Variant names:

• chr9-68537489-C-T
• rs770609895
• NM_153237.2:c.283G>A

Variant summary

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

The NM_153237.2(TMEM252):​c.283G>A​(p.Asp95Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000387 in 1,600,502 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: TMEM252 NM_153237.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45
• Publications: 0 publications found

Genes affected

TMEM252 (HGNC:28537): (transmembrane protein 252) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LINC01506 (HGNC:51187): (long intergenic non-protein coding RNA 1506)

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=0.13700095).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153237.2. 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
	TMEM252	NM_153237.2	MANE Select	c.283G>A	p.Asp95Asn	missense	Exon 2 of 2	NP_694969.1	Q8N6L7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMEM252	ENST00000377311.4	TSL:1 MANE Select	c.283G>A	p.Asp95Asn	missense	Exon 2 of 2	ENSP00000366528.4	Q8N6L7
	LINC01506	ENST00000762445.1		n.217+8012G>A		intron	N/A
	LINC01506	ENST00000762446.1		n.200+8012G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152234 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000507 AC: 12 AN: 236794 AF XY: 0.0000624

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000280

Gnomad NFE exome AF: 0.0000457

Gnomad OTH exome AF: 0.000174

GnomAD4 exome AF: 0.0000380 AC: 55 AN: 1448268 Hom.: 0 Cov.: 31 AF XY: 0.0000417 AC XY: 30 AN XY: 720240

African (AFR) AF: 0.00 AC: 0 AN: 32500

American (AMR) AF: 0.00 AC: 0 AN: 40650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25654

East Asian (EAS) AF: 0.00 AC: 0 AN: 39332

South Asian (SAS) AF: 0.00 AC: 0 AN: 83098

European-Finnish (FIN) AF: 0.000319 AC: 17 AN: 53326

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.0000325 AC: 36 AN: 1108108

Other (OTH) AF: 0.0000334 AC: 2 AN: 59878

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152234 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74380

African (AFR) AF: 0.00 AC: 0 AN: 41472

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

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

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10620

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68036

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

Alfa AF: 0.000172 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000330 AC: 4

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	0.12
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Benign	0.090
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.4
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.37
Sift	Benign	0.10	T
Sift4G	Benign	0.088	T
Polyphen		0.51	P
Vest4		0.15
MVP		0.030
MPC		0.15
ClinPred		0.50	D
GERP RS		3.0
Varity_R		0.20
gMVP		0.46
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs770609895; hg19: chr9-71152405; COSMIC: COSV104692914; COSMIC: COSV104692914;