NM_004227.4:c.*1840C>A

Variant names:

• chr7-6163104-G-T
• rs17136052
• NM_004227.4:c.*1840C>A

Variant summary

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

The NM_004227.4(CYTH3):​c.*1840C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,708 control chromosomes in the GnomAD database, including 2,095 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 0.16 (2091 hom., cov: 33)
  • Exomes 𝑓: 0.17 (4 hom.)
• Consequence: CYTH3 NM_004227.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 7 publications found

Genes affected

CYTH3 (HGNC:9504): (cytohesin 3) This gene encodes a member of the PSCD (pleckstrin homology, Sec7 and coiled-coil domains) family. PSCD family members 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 (GEP) 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 encoded protein is involved in the control of Golgi structure and function, and it may have a physiological role in regulating ADP-ribosylation factor protein 6 (ARF) functions, in addition to acting on ARF1. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYTH3	NM_004227.4	c.*1840C>A		3_prime_UTR_variant	Exon 13 of 13	ENST00000350796.8	NP_004218.1
CYTH3	NM_001367580.1	c.*1840C>A		3_prime_UTR_variant	Exon 13 of 13		NP_001354509.1
CYTH3	NM_001367581.1	c.*1840C>A		3_prime_UTR_variant	Exon 14 of 14		NP_001354510.1
CYTH3	NM_001367582.1	c.*1840C>A		3_prime_UTR_variant	Exon 8 of 8		NP_001354511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYTH3	ENST00000350796.8	c.*1840C>A		3_prime_UTR_variant	Exon 13 of 13	1	NM_004227.4	ENSP00000297044.7

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23965 AN: 152154 Hom.: 2090 Cov.: 33

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.00828

Gnomad SAS AF: 0.0594

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.174 AC: 76 AN: 436 Hom.: 4 Cov.: 0 AF XY: 0.173 AC XY: 46 AN XY: 266

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.176 AC: 72 AN: 408

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.150 AC: 3 AN: 20

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.157 AC: 23979 AN: 152272 Hom.: 2091 Cov.: 33 AF XY: 0.154 AC XY: 11467 AN XY: 74460

African (AFR) AF: 0.213 AC: 8843 AN: 41550

American (AMR) AF: 0.146 AC: 2238 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3472

East Asian (EAS) AF: 0.00829 AC: 43 AN: 5184

South Asian (SAS) AF: 0.0607 AC: 293 AN: 4830

European-Finnish (FIN) AF: 0.140 AC: 1486 AN: 10600

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10186 AN: 68014

Other (OTH) AF: 0.154 AC: 325 AN: 2116

Alfa AF: 0.138 Hom.: 1176

Bravo AF: 0.162

Asia WGS AF: 0.0460 AC: 159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.7
DANN	Benign	0.74
PhyloP100		1.1
Mutation Taster		=99/1	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: rs17136052; hg19: chr7-6202735;