6-109368871-G-A

Variant names:

• chr6-109368871-G-A
• rs876661402
• NM_006016.6:c.574C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006016.6(CD164):​c.574C>T​(p.Arg192*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000137 in 1,460,578 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as no classifications from unflagged records (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CD164 NM_006016.6 stop_gained
• Clinical Significance: no classifications from unflagged records no classifications from unflagged records P:2
• Conservation: PhyloP100: 4.84
• Publications: 2 publications found

Genes affected

CD164 (HGNC:1632): (CD164 molecule) This gene encodes a transmembrane sialomucin and cell adhesion molecule that regulates the proliferation, adhesion and migration of hematopoietic progenitor cells. The encoded protein also interacts with the C-X-C chemokine receptor type 4 and may regulate muscle development. Elevated expression of this gene has been observed in human patients with Sezary syndrome, a type of blood cancer, and a mutation in this gene may be associated with impaired hearing. [provided by RefSeq, Oct 2016]

CD164 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet
• autosomal dominant nonsyndromic hearing loss 66

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006016.6. 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
	CD164	NM_006016.6	MANE Select	c.574C>T	p.Arg192*	stop_gained	Exon 6 of 6	NP_006007.2
	CD164	NM_001142401.3		c.535C>T	p.Arg179*	stop_gained	Exon 5 of 5	NP_001135873.1
	CD164	NM_001142402.3		c.517C>T	p.Arg173*	stop_gained	Exon 5 of 5	NP_001135874.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD164	ENST00000310786.10	TSL:1 MANE Select	c.574C>T	p.Arg192*	stop_gained	Exon 6 of 6	ENSP00000309376.4
	CD164	ENST00000275080.11	TSL:1	c.535C>T	p.Arg179*	stop_gained	Exon 5 of 5	ENSP00000275080.7
	CD164	ENST00000324953.9	TSL:1	c.517C>T	p.Arg173*	stop_gained	Exon 5 of 5	ENSP00000314177.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460578 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726654

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33368

American (AMR) AF: 0.00 AC: 0 AN: 44344

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111544

Other (OTH) AF: 0.00 AC: 0 AN: 60316

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000000770867), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000613 Hom.: 0

ClinVar

Significance: no classifications from unflagged records

Submissions summary: Pathogenic:2

Revision: no classifications from unflagged records

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 66 Pathogenic:2

Jan 07, 2023

Baylor Genetics

Significance: Likely pathogenic

Review Status: flagged submission

Collection Method: clinical testing

Jul 30, 2019

OMIM

Significance: Pathogenic

Review Status: flagged submission

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.54	D
BayesDel_noAF	Pathogenic	0.54
CADD	Pathogenic	38
DANN	Uncertain	0.99
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.90	D
PhyloP100		4.8
Vest4		0.51
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=1/199	disease causing (ClinVar)

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: rs876661402; hg19: chr6-109690074;