NM_006016.6:c.362A>C

Variant names:

• chr6-109376082-T-G
• rs771601649
• NM_006016.6:c.362A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006016.6(CD164):​c.362A>C​(p.Asn121Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,418,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N121I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CD164 NM_006016.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 0 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: MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• autosomal dominant nonsyndromic hearing loss 66

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13758549).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD164	NM_006016.6	MANE Select	c.362A>C	p.Asn121Thr	missense	Exon 4 of 6	NP_006007.2
	CD164	NM_001142403.3		c.362A>C	p.Asn121Thr	missense	Exon 4 of 7	NP_001135875.1	Q04900-2
	CD164	NM_001142402.3		c.362A>C	p.Asn121Thr	missense	Exon 4 of 5	NP_001135874.1	Q04900-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD164	ENST00000310786.10	TSL:1 MANE Select	c.362A>C	p.Asn121Thr	missense	Exon 4 of 6	ENSP00000309376.4	Q04900-1
	CD164	ENST00000413644.6	TSL:1	c.362A>C	p.Asn121Thr	missense	Exon 4 of 7	ENSP00000402237.2	Q04900-2
	CD164	ENST00000324953.9	TSL:1	c.362A>C	p.Asn121Thr	missense	Exon 4 of 5	ENSP00000314177.5	Q04900-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1418328 Hom.: 0 Cov.: 28 AF XY: 0.00000142 AC XY: 1 AN XY: 705716

⚠️ 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: 30334

American (AMR) AF: 0.00 AC: 0 AN: 29922

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24708

East Asian (EAS) AF: 0.00 AC: 0 AN: 37880

South Asian (SAS) AF: 0.00 AC: 0 AN: 77600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52826

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5598

European-Non Finnish (NFE) AF: 9.08e-7 AC: 1 AN: 1100936

Other (OTH) AF: 0.00 AC: 0 AN: 58524

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.045	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.19
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.039
Sift	Benign	0.032	D
Sift4G	Benign	0.58	T
Polyphen		0.077	B
Vest4		0.17
MutPred		0.48		Gain of glycosylation at N121 (P = 0.0014)
MVP		0.44
MPC		0.30
ClinPred		0.71	D
GERP RS		-0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.32
Mutation Taster		=85/15	polymorphism

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: rs771601649; hg19: chr6-109697285;