chr6-109376082-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_006016.6(CD164):​c.362A>G​(p.Asn121Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000866 in 1,570,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). 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: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000085 (0 hom.)
• Consequence: CD164 NM_006016.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.190
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05463636).
• BS2: High AC in GnomAd4 at 15 Unknown,AD gene.

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>G	p.Asn121Ser	missense	Exon 4 of 6	NP_006007.2
	CD164	NM_001142403.3		c.362A>G	p.Asn121Ser	missense	Exon 4 of 7	NP_001135875.1	Q04900-2
	CD164	NM_001142402.3		c.362A>G	p.Asn121Ser	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>G	p.Asn121Ser	missense	Exon 4 of 6	ENSP00000309376.4	Q04900-1
	CD164	ENST00000413644.6	TSL:1	c.362A>G	p.Asn121Ser	missense	Exon 4 of 7	ENSP00000402237.2	Q04900-2
	CD164	ENST00000324953.9	TSL:1	c.362A>G	p.Asn121Ser	missense	Exon 4 of 5	ENSP00000314177.5	Q04900-4

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152204 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000863 AC: 18 AN: 208460 AF XY: 0.0000700

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000246

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000117

Gnomad OTH exome AF: 0.000204

GnomAD4 exome AF: 0.0000853 AC: 121 AN: 1418322 Hom.: 0 Cov.: 28 AF XY: 0.0000879 AC XY: 62 AN XY: 705714

African (AFR) AF: 0.00 AC: 0 AN: 30334

American (AMR) AF: 0.000201 AC: 6 AN: 29922

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

East Asian (EAS) AF: 0.0000264 AC: 1 AN: 37880

South Asian (SAS) AF: 0.0000515 AC: 4 AN: 77598

European-Finnish (FIN) AF: 0.0000379 AC: 2 AN: 52826

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

European-Non Finnish (NFE) AF: 0.0000936 AC: 103 AN: 1100932

Other (OTH) AF: 0.0000854 AC: 5 AN: 58524

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152204 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74360

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.000523 AC: 8 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68030

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.0000894 Hom.: 0

Bravo AF: 0.000128

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000778 AC: 3

ExAC AF: 0.0000741 AC: 9

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.19
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.053
Sift	Benign	0.29	T
Sift4G	Benign	0.58	T
Polyphen		0.035	B
Vest4		0.16
MVP		0.33
MPC		0.27
ClinPred		0.054	T
GERP RS		-0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.038
gMVP		0.24
Mutation Taster		=89/11	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;