rs750453605

Variant names:

• chr16-66566526-C-T
• rs750453605
• NM_052999.4:c.13C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-66566526-C-T
• chr16-66566526-C-A
• chr16-66566526-C-G

Variant summary

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

The NM_052999.4(CMTM1):​c.13C>T​(p.His5Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,455,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 0.000018 (0 hom.)
• Consequence: CMTM1 NM_052999.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.28
• Publications: 10 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]

ENSG00000277978 (HGNC:):

CKLF (HGNC:13253): (chemokine like factor) The product of this gene is a cytokine. Cytokines are small proteins that have an essential role in the immune and inflammatory responses. This gene is one of several chemokine-like factor genes located in a cluster on chromosome 16. The protein encoded by this gene is a potent chemoattractant for neutrophils, monocytes and lymphocytes. It also can stimulate the proliferation of skeletal muscle cells. This protein may play important roles in inflammation and in the regeneration of skeletal muscle. Alternatively spliced transcript variants encoding different isoforms have been identified. Naturally occurring read-through transcription occurs between this locus and the neighboring locus CMTM1 (CKLF-like MARVEL transmembrane domain containing 1).[provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03063637).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052999.4. 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
	CMTM1	NM_052999.4	MANE Select	c.13C>T	p.His5Tyr	missense	Exon 1 of 4	NP_443725.3
	CMTM1	NM_181268.3		c.13C>T	p.His5Tyr	missense	Exon 1 of 4	NP_851785.2	E9PAX0
	CMTM1	NM_181269.3		c.13C>T	p.His5Tyr	missense	Exon 1 of 4	NP_851786.1	Q8IZ96-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CMTM1	ENST00000379500.7	TSL:1 MANE Select	c.13C>T	p.His5Tyr	missense	Exon 1 of 4	ENSP00000368814.2	Q8IZ96-17
	CMTM1	ENST00000533953.5	TSL:1	c.13C>T	p.His5Tyr	missense	Exon 1 of 3	ENSP00000435786.1	E9PIL3
	CMTM1	ENST00000328020.10	TSL:1	c.13C>T	p.His5Tyr	missense	Exon 1 of 4	ENSP00000330061.6	E9PAX0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000529 AC: 13 AN: 245660 AF XY: 0.0000828

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000179 AC: 26 AN: 1455596 Hom.: 0 Cov.: 32 AF XY: 0.0000235 AC XY: 17 AN XY: 723932

African (AFR) AF: 0.00 AC: 0 AN: 33330

American (AMR) AF: 0.00 AC: 0 AN: 44150

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25656

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39668

South Asian (SAS) AF: 0.000268 AC: 23 AN: 85686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109238

Other (OTH) AF: 0.0000333 AC: 2 AN: 60150

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000659 AC: 8

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	0.10
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.014
DANN	Benign	0.61
DEOGEN2	Benign	0.038	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.031	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.3
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.052
Sift	Benign	0.071	T
Sift4G	Uncertain	0.060	T
Polyphen		0.075	B
Vest4		0.14
MutPred		0.11		Gain of phosphorylation at H5 (P = 4e-04)
MVP		0.20
MPC		0.35
ClinPred		0.039	T
GERP RS		-3.8
PromoterAI		0.021	Neutral
Varity_R		0.027
gMVP		0.047
Mutation Taster		=98/2	polymorphism

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: rs750453605; hg19: chr16-66600429;