chr14-58138232-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001001872.4(ARMH4):​c.1127C>T​(p.Thr376Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000762 in 1,613,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

ARMH4
NM_001001872.4 missense

Scores

17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.159
Variant links:
Genes affected
ARMH4 (HGNC:19846): (armadillo like helical domain containing 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.029791236).
BP6
Variant 14-58138232-G-A is Benign according to our data. Variant chr14-58138232-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3129714.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ARMH4NM_001001872.4 linkuse as main transcriptc.1127C>T p.Thr376Met missense_variant 2/8 ENST00000267485.7 NP_001001872.2
ARMH4NM_001320173.3 linkuse as main transcriptc.1127C>T p.Thr376Met missense_variant 2/5 NP_001307102.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ARMH4ENST00000267485.7 linkuse as main transcriptc.1127C>T p.Thr376Met missense_variant 2/81 NM_001001872.4 ENSP00000267485 P1Q86TY3-1
ARMH4ENST00000334342.5 linkuse as main transcriptn.1292C>T non_coding_transcript_exon_variant 2/51
ARMH4ENST00000557175.5 linkuse as main transcriptn.894+116C>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152190
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000955
AC:
24
AN:
251406
Hom.:
0
AF XY:
0.000110
AC XY:
15
AN XY:
135878
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.000260
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000753
AC:
110
AN:
1461784
Hom.:
0
Cov.:
32
AF XY:
0.0000880
AC XY:
64
AN XY:
727204
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000746
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152190
Hom.:
0
Cov.:
33
AF XY:
0.0000538
AC XY:
4
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.0000965
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000102
Hom.:
0
Bravo
AF:
0.0000869
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsNov 12, 2021This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.071
BayesDel_addAF
Benign
-0.49
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
0.040
DANN
Benign
0.72
DEOGEN2
Benign
0.00077
T
Eigen
Benign
-1.9
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.034
N
LIST_S2
Benign
0.42
T
M_CAP
Benign
0.0074
T
MetaRNN
Benign
0.030
T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N
PROVEAN
Benign
-0.020
N
REVEL
Benign
0.038
Sift
Benign
0.28
T
Sift4G
Benign
0.25
T
Polyphen
0.14
B
Vest4
0.14
MVP
0.014
MPC
0.034
ClinPred
0.0090
T
GERP RS
-8.8
Varity_R
0.0072
gMVP
0.057

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: rs367838185; hg19: chr14-58604950; COSMIC: COSV50771016; COSMIC: COSV50771016; API