rs2304970

Variant names:

• chr17-4739492-C-A
• rs2304970
• NM_001386809.1:c.-153G>T

Your query was ambiguous. Multiple possible variants found:

• chr17-4739492-C-A
• chr17-4739492-C-G

Variant summary

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

The NM_001386809.1(CXCL16):​c.-153G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 1,125,220 control chromosomes in the GnomAD database, including 171,660 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 0.56 (23637 hom., cov: 34)
  • Exomes 𝑓: 0.55 (148023 hom.)
• Consequence: CXCL16 NM_001386809.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 7 publications found

Genes affected

CXCL16 (HGNC:16642): (C-X-C motif chemokine ligand 16) Enables chemokine activity. Involved in several processes, including positive regulation of cell growth; response to interferon-gamma; and response to tumor necrosis factor. Located in extracellular space. Biomarker of COVID-19 and systemic scleroderma. [provided by Alliance of Genome Resources, Apr 2022]

ZMYND15 (HGNC:20997): (zinc finger MYND-type containing 15) This gene encodes a MYND-containing zinc-binding protein with a nuclear localization sequence. A similar gene in mice has been shown to act as a testis-specific transcriptional repressor by recruiting histone deacetylase enzymes to regulate spatiotemporal expression of many haploid genes. This protein may play an important role in spermatogenesis. Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jun 2012]

ZMYND15 Gene-Disease associations (from GenCC):

• spermatogenic failure 14

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386809.1. 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
	CXCL16	NM_001386809.1	MANE Select	c.-153G>T		5_prime_UTR	Exon 1 of 6	NP_001373738.1	Q9H2A7
	CXCL16	NM_001100812.2		c.-153G>T		5_prime_UTR	Exon 1 of 5	NP_001094282.2	Q9H2A7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL16	ENST00000293778.12	TSL:1 MANE Select	c.-153G>T		5_prime_UTR	Exon 1 of 6	ENSP00000293778.7	Q9H2A7
	CXCL16	ENST00000574412.6	TSL:1	c.-153G>T		5_prime_UTR	Exon 1 of 5	ENSP00000459592.2	Q9H2A7
	ZMYND15	ENST00000885791.1		c.-556C>A		5_prime_UTR	Exon 1 of 14	ENSP00000555850.1

Frequencies

GnomAD3 genomes AF: 0.556 AC: 84551 AN: 151946 Hom.: 23612 Cov.: 34

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.590

GnomAD4 exome AF: 0.548 AC: 533334 AN: 973156 Hom.: 148023 Cov.: 13 AF XY: 0.551 AC XY: 273685 AN XY: 496866

African (AFR) AF: 0.557 AC: 12754 AN: 22892

American (AMR) AF: 0.614 AC: 18763 AN: 30536

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 13029 AN: 21318

East Asian (EAS) AF: 0.578 AC: 19669 AN: 34026

South Asian (SAS) AF: 0.596 AC: 42094 AN: 70676

European-Finnish (FIN) AF: 0.525 AC: 18298 AN: 34878

Middle Eastern (MID) AF: 0.569 AC: 1796 AN: 3156

European-Non Finnish (NFE) AF: 0.537 AC: 382503 AN: 711896

Other (OTH) AF: 0.558 AC: 24428 AN: 43778

GnomAD4 genome AF: 0.557 AC: 84633 AN: 152064 Hom.: 23637 Cov.: 34 AF XY: 0.558 AC XY: 41507 AN XY: 74330

African (AFR) AF: 0.557 AC: 23116 AN: 41512

American (AMR) AF: 0.621 AC: 9488 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2145 AN: 3464

East Asian (EAS) AF: 0.601 AC: 3078 AN: 5120

South Asian (SAS) AF: 0.590 AC: 2842 AN: 4820

European-Finnish (FIN) AF: 0.520 AC: 5517 AN: 10600

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36645 AN: 67944

Other (OTH) AF: 0.590 AC: 1245 AN: 2110

Alfa AF: 0.467 Hom.: 1888

Bravo AF: 0.564

Asia WGS AF: 0.616 AC: 2144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.3
DANN	Benign	0.74
PhyloP100		-1.5
PromoterAI		-0.0038	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2304970;

hg19: chr17-4642787;