16-66566599-G-C

Variant names:

• chr16-66566599-G-C
• NM_052999.4:c.86G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052999.4(CMTM1):​c.86G>C​(p.Ser29Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. 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. S29N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CMTM1 NM_052999.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06615117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CMTM1	NM_052999.4	c.86G>C	p.Ser29Thr	missense_variant	Exon 1 of 4	ENST00000379500.7	NP_443725.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CMTM1	ENST00000379500.7	c.86G>C	p.Ser29Thr	missense_variant	Exon 1 of 4	1	NM_052999.4	ENSP00000368814.2
CKLF-CMTM1	ENST00000616804.5	c.237+8251G>C		intron_variant	Intron 2 of 3	2		ENSP00000479319.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461828 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.9
DANN	Benign	0.70
DEOGEN2	Benign	0.013	.;T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.25	T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.066	T;T;T;T
MetaSVM	Benign	-0.93	T
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.35	N;N;N;N
REVEL	Benign	0.065
Sift	Benign	0.47	T;T;T;T
Sift4G	Benign	0.68	T;T;T;T
Polyphen		0.61	P;P;.;P
Vest4		0.12
MutPred		0.080		Loss of phosphorylation at S29 (P = 0.0636);Loss of phosphorylation at S29 (P = 0.0636);Loss of phosphorylation at S29 (P = 0.0636);Loss of phosphorylation at S29 (P = 0.0636);
MVP		0.076
MPC		0.71
ClinPred		0.12	T
GERP RS		-5.1
gMVP		0.052

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-66600502;