chr6-109376082-T-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM1BP4_StrongBS2

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. 15/21 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

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.190
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PM1
In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity MUC24_HUMAN
BP4
Computational evidence support a benign effect (MetaRNN=0.05463636).
BS2
High AC in GnomAd4 at 15 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CD164NM_006016.6 linkc.362A>G p.Asn121Ser missense_variant Exon 4 of 6 ENST00000310786.10 NP_006007.2 Q04900-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CD164ENST00000310786.10 linkc.362A>G p.Asn121Ser missense_variant Exon 4 of 6 1 NM_006016.6 ENSP00000309376.4 Q04900-1

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152204
Hom.:
0
Cov.:
32
show subpopulations
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
GnomAD3 exomes
AF:
0.0000863
AC:
18
AN:
208460
Hom.:
0
AF XY:
0.0000700
AC XY:
8
AN XY:
114260
show subpopulations
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 SAS 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
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000264
Gnomad4 SAS exome
AF:
0.0000515
Gnomad4 FIN exome
AF:
0.0000379
Gnomad4 NFE exome
AF:
0.0000936
Gnomad4 OTH exome
AF:
0.0000854
GnomAD4 genome
AF:
0.0000986
AC:
15
AN:
152204
Hom.:
0
Cov.:
32
AF XY:
0.000121
AC XY:
9
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000523
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.000478
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

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Dec 31, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 121 of the CD164 protein (p.Asn121Ser). This variant is present in population databases (rs771601649, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CD164-related conditions. ClinVar contains an entry for this variant (Variation ID: 2174800). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Probably Damaging". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

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;T;T;T;T
M_CAP
Benign
0.0084
T
MetaRNN
Benign
0.055
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
.;L;L;L;L
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-1.6
N;N;N;N;D
REVEL
Benign
0.053
Sift
Benign
0.29
T;T;T;T;D
Sift4G
Benign
0.58
T;T;T;T;T
Polyphen
0.035, 0.043, 0.15
.;B;B;B;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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs771601649; hg19: chr6-109697285; API