rs11436

Variant names:

• chr1-31364473-T-C
• rs11436
• NM_016505.4:c.*280T>C

Variant summary

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

The NM_016505.4(ZCCHC17):​c.*280T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 453,152 control chromosomes in the GnomAD database, including 73,108 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 0.54 (23364 hom., cov: 31)
  • Exomes 𝑓: 0.56 (49744 hom.)
• Consequence: ZCCHC17 NM_016505.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.911
• Publications: 16 publications found

Genes affected

ZCCHC17 (HGNC:30246): (zinc finger CCHC-type containing 17) Enables identical protein binding activity. Predicted to be involved in RNA stabilization. Predicted to be located in nucleolus. Predicted to be part of cytosolic large ribosomal subunit. [provided by Alliance of Genome Resources, Apr 2022]

FABP3 (HGNC:3557): (fatty acid binding protein 3) The intracellular fatty acid-binding proteins (FABPs) belongs to a multigene family. FABPs are divided into at least three distinct types, namely the hepatic-, intestinal- and cardiac-type. They form 14-15 kDa proteins and are thought to participate in the uptake, intracellular metabolism and/or transport of long-chain fatty acids. They may also be responsible in the modulation of cell growth and proliferation. Fatty acid-binding protein 3 gene contains four exons and its function is to arrest growth of mammary epithelial cells. This gene is a candidate tumor suppressor gene for human breast cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZCCHC17	NM_016505.4	c.*280T>C		3_prime_UTR_variant	Exon 8 of 8	ENST00000344147.10	NP_057589.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZCCHC17	ENST00000344147.10	c.*280T>C		3_prime_UTR_variant	Exon 8 of 8	1	NM_016505.4	ENSP00000343557.5

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82650 AN: 151906 Hom.: 23365 Cov.: 31

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.641

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.558

GnomAD4 exome AF: 0.557 AC: 167823 AN: 301128 Hom.: 49744 Cov.: 4 AF XY: 0.552 AC XY: 85121 AN XY: 154342

African (AFR) AF: 0.461 AC: 4708 AN: 10208

American (AMR) AF: 0.529 AC: 6351 AN: 12008

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 6397 AN: 9798

East Asian (EAS) AF: 0.175 AC: 4055 AN: 23222

South Asian (SAS) AF: 0.357 AC: 7055 AN: 19748

European-Finnish (FIN) AF: 0.574 AC: 11682 AN: 20362

Middle Eastern (MID) AF: 0.589 AC: 795 AN: 1350

European-Non Finnish (NFE) AF: 0.625 AC: 116598 AN: 186450

Other (OTH) AF: 0.566 AC: 10182 AN: 17982

GnomAD4 genome AF: 0.544 AC: 82656 AN: 152024 Hom.: 23364 Cov.: 31 AF XY: 0.535 AC XY: 39778 AN XY: 74340

African (AFR) AF: 0.461 AC: 19103 AN: 41440

American (AMR) AF: 0.554 AC: 8469 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.641 AC: 2223 AN: 3468

East Asian (EAS) AF: 0.191 AC: 990 AN: 5170

South Asian (SAS) AF: 0.351 AC: 1687 AN: 4800

European-Finnish (FIN) AF: 0.573 AC: 6054 AN: 10564

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.623 AC: 42323 AN: 67976

Other (OTH) AF: 0.554 AC: 1169 AN: 2112

Alfa AF: 0.603 Hom.: 14208

Bravo AF: 0.540

Asia WGS AF: 0.283 AC: 987 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	15
DANN	Benign	0.84
PhyloP100		0.91
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11436; hg19: chr1-31837320; COSMIC: COSV60001538; COSMIC: COSV60001538;