NM_052999.4:c.591+3191A>G

Variant names:

• chr16-66573285-A-G
• rs896086
• NM_052999.4:c.591+3191A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052999.4(CMTM1):​c.591+3191A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,174 control chromosomes in the GnomAD database, including 5,965 homozygotes. 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 0.25 (5965 hom., cov: 32)
• Consequence: CMTM1 NM_052999.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.889
• Publications: 14 publications found

Genes affected

CMTM1 (HGNC:19172): (CKLF like MARVEL transmembrane domain containing 1) This gene belongs to the chemokine-like factor gene superfamily, a novel family that is similar to the chemokine and the transmembrane 4 superfamilies of signaling molecules. The protein encoded by this gene may play an important role in testicular development. Alternatively spliced transcript variants encoding different isoforms have been identified. Naturally occurring read-through transcription occurs between this locus and the neighboring locus CKLF (chemokine-like factor).[provided by RefSeq, Feb 2011]

CKLF-CMTM1 (HGNC:39977): (CKLF-CMTM1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring CKLF (chemokine-like factor) and CMTM1 (CKLF-like MARVEL transmembrane domain containing 1) genes on chromosome 16. The read-through transcript produces a fusion protein that shares sequence identity with each individual gene product. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMTM1	NM_052999.4	c.591+3191A>G		intron_variant	Intron 2 of 3	ENST00000379500.7	NP_443725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMTM1	ENST00000379500.7	c.591+3191A>G		intron_variant	Intron 2 of 3	1	NM_052999.4	ENSP00000368814.2
CKLF-CMTM1	ENST00000616804.5	c.238-3819A>G		intron_variant	Intron 2 of 3	2		ENSP00000479319.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38089 AN: 152056 Hom.: 5963 Cov.: 32

Gnomad AFR AF: 0.0621

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.276

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.250 AC: 38086 AN: 152174 Hom.: 5965 Cov.: 32 AF XY: 0.254 AC XY: 18928 AN XY: 74398

African (AFR) AF: 0.0619 AC: 2573 AN: 41554

American (AMR) AF: 0.285 AC: 4349 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.401 AC: 1392 AN: 3470

East Asian (EAS) AF: 0.390 AC: 2019 AN: 5180

South Asian (SAS) AF: 0.292 AC: 1408 AN: 4814

European-Finnish (FIN) AF: 0.347 AC: 3672 AN: 10572

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21654 AN: 67990

Other (OTH) AF: 0.279 AC: 589 AN: 2112

Alfa AF: 0.290 Hom.: 15070

Bravo AF: 0.236

Asia WGS AF: 0.316 AC: 1098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.74
PhyloP100		-0.89
Mutation Taster		=100/0	polymorphism (auto)

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: rs896086; hg19: chr16-66607188;