NM_001386809.1:c.80-7C>T

Variant names:

• chr17-4738927-G-A
• rs2304973
• NM_001386809.1:c.80-7C>T

Variant summary

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

The NM_001386809.1(CXCL16):​c.80-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.087 in 1,612,952 control chromosomes in the GnomAD database, including 7,133 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.076 (529 hom., cov: 30)
  • Exomes 𝑓: 0.088 (6604 hom.)
• Consequence: CXCL16 NM_001386809.1 splice_region, intron
• Scores: Splicing: ADA: 0.00002511
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 19 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.165 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL16	NM_001386809.1	MANE Select	c.80-7C>T		splice_region intron	N/A	NP_001373738.1
	CXCL16	NM_001100812.2		c.80-7C>T		splice_region intron	N/A	NP_001094282.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL16	ENST00000293778.12	TSL:1 MANE Select	c.80-7C>T		splice_region intron	N/A	ENSP00000293778.7
	CXCL16	ENST00000574412.6	TSL:1	c.80-7C>T		splice_region intron	N/A	ENSP00000459592.2
	CXCL16	ENST00000573123.1	TSL:2	c.-90C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000460145.1

Frequencies

GnomAD3 genomes AF: 0.0764 AC: 11598 AN: 151800 Hom.: 527 Cov.: 30

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0848

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0852

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0805

Gnomad OTH AF: 0.0947

GnomAD2 exomes AF: 0.0989 AC: 24768 AN: 250372 AF XY: 0.105

Gnomad AFR exome AF: 0.0350

Gnomad AMR exome AF: 0.0899

Gnomad ASJ exome AF: 0.159

Gnomad EAS exome AF: 0.0781

Gnomad FIN exome AF: 0.107

Gnomad NFE exome AF: 0.0820

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.0881 AC: 128716 AN: 1461034 Hom.: 6604 Cov.: 36 AF XY: 0.0918 AC XY: 66700 AN XY: 726828

African (AFR) AF: 0.0359 AC: 1201 AN: 33472

American (AMR) AF: 0.0912 AC: 4075 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 4090 AN: 26066

East Asian (EAS) AF: 0.0792 AC: 3142 AN: 39692

South Asian (SAS) AF: 0.186 AC: 16072 AN: 86206

European-Finnish (FIN) AF: 0.104 AC: 5548 AN: 53328

Middle Eastern (MID) AF: 0.162 AC: 934 AN: 5766

European-Non Finnish (NFE) AF: 0.0793 AC: 88109 AN: 1111472

Other (OTH) AF: 0.0919 AC: 5545 AN: 60354

GnomAD4 genome AF: 0.0764 AC: 11603 AN: 151918 Hom.: 529 Cov.: 30 AF XY: 0.0794 AC XY: 5893 AN XY: 74252

African (AFR) AF: 0.0389 AC: 1614 AN: 41438

American (AMR) AF: 0.0847 AC: 1294 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 532 AN: 3468

East Asian (EAS) AF: 0.0848 AC: 437 AN: 5152

South Asian (SAS) AF: 0.175 AC: 838 AN: 4780

European-Finnish (FIN) AF: 0.109 AC: 1147 AN: 10540

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0805 AC: 5472 AN: 67948

Other (OTH) AF: 0.0933 AC: 197 AN: 2112

Alfa AF: 0.0843 Hom.: 1268

Bravo AF: 0.0710

Asia WGS AF: 0.122 AC: 426 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.45
DANN	Benign	0.80
PhyloP100		-1.1
PromoterAI		0.071	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000025
dbscSNV1_RF	Benign	0.0040
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: rs2304973; hg19: chr17-4642222; COSMIC: COSV52641918; COSMIC: COSV52641918;