rs777499031

Variant names:

• chr17-78702597-T-A
• NM_004762.6:c.178A>T

Your query was ambiguous. Multiple possible variants found:

• chr17-78702597-T-A
• chr17-78702597-T-C
• chr17-78702597-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004762.6(CYTH1):​c.178A>T​(p.Met60Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CYTH1 NM_004762.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.99

Genes affected

CYTH1 (HGNC:9501): (cytohesin 1) The protein encoded by this gene is a member of the PSCD family. Members of this family have identical structural organization that consists of an N-terminal coiled-coil motif, a central Sec7 domain, and a C-terminal pleckstrin homology (PH) domain. The coiled-coil motif is involved in homodimerization, the Sec7 domain contains guanine-nucleotide exchange protein activity, and the PH domain interacts with phospholipids and is responsible for association of PSCDs with membranes. Members of this family appear to mediate the regulation of protein sorting and membrane trafficking. This gene is highly expressed in natural killer and peripheral T cells, and regulates the adhesiveness of integrins at the plasma membrane of lymphocytes. A pseudogene of this gene has been defined on the X chromosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24635085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYTH1	NM_004762.6	c.178A>T	p.Met60Leu	missense_variant	Exon 4 of 14	ENST00000446868.8	NP_004753.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYTH1	ENST00000446868.8	c.178A>T	p.Met60Leu	missense_variant	Exon 4 of 14	5	NM_004762.6	ENSP00000389095.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461864 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.15	.;.;.;T;T;.;.;.;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.059
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	.;D;T;.;T;T;T;D;D
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.25	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.60	.;.;N;N;N;.;.;.;.
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.47	.;.;.;N;N;.;.;.;.
REVEL	Benign	0.078
Sift	Benign	0.39	.;.;.;T;T;.;.;.;.
Sift4G	Benign	1.0	T;T;T;T;T;.;.;T;.
Polyphen		0.0	.;.;B;B;B;.;.;.;.
Vest4		0.56
MutPred		0.50		.;.;Loss of methylation at K64 (P = 0.0814);Loss of methylation at K64 (P = 0.0814);Loss of methylation at K64 (P = 0.0814);.;.;.;.;
MVP		0.33
MPC		0.57
ClinPred		0.75	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.35

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-76698679;