Genetic Variant FAM110D:p.Arg240Cys (chr1-26162009-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024869.3(FAM110D):c.718C>T(p.Arg240Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000445 in 1,235,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

FAM110D
NM_024869.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.57

Publications

0 publications found

Variant links:

Genes affected

FAM110D (HGNC:25860): (family with sequence similarity 110 member D)

FAM110D links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11947325).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024869.3. 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
	FAM110D	NM_024869.3	MANE Select	c.718C>T	p.Arg240Cys	missense	Exon 2 of 2	NP_079145.2	Q8TAY7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM110D	ENST00000374268.5	TSL:1 MANE Select	c.718C>T	p.Arg240Cys	missense	Exon 2 of 2	ENSP00000363386.3	Q8TAY7
FAM110D	ENST00000880266.1		c.718C>T	p.Arg240Cys	missense	Exon 3 of 3	ENSP00000550325.1
FAM110D	ENST00000880267.1		c.718C>T	p.Arg240Cys	missense	Exon 3 of 3	ENSP00000550326.1

Frequencies

GnomAD3 genomes

AF:

0.000238

AC:

AN:

151396

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000822

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.000968

GnomAD4 exome

AF:

0.0000175

AC:

AN:

1084200

Hom.:

Cov.:

AF XY:

0.0000194

AC XY:

AN XY:

515198

show subpopulations

African (AFR)

AF:

0.000622

AC:

AN:

22512

American (AMR)

AF:

0.00

AC:

AN:

8072

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13864

East Asian (EAS)

AF:

0.00

AC:

AN:

25922

South Asian (SAS)

AF:

0.00

AC:

AN:

20692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21336

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3166

European-Non Finnish (NFE)

AF:

0.00000432

AC:

AN:

925256

Other (OTH)

AF:

0.0000231

AC:

AN:

43380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000238

AC:

AN:

151504

Hom.:

Cov.:

AF XY:

0.000270

AC XY:

AN XY:

74022

show subpopulations

African (AFR)

AF:

0.000820

AC:

AN:

41468

American (AMR)

AF:

0.00

AC:

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67812

Other (OTH)

AF:

0.000958

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000242

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.013

Eigen

Benign

0.079

Eigen_PC

Benign

0.0011

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.74

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.69

PhyloP100

1.6

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.80

REVEL

Benign

0.16

Sift

Benign

0.034

Sift4G

Uncertain

0.049

Polyphen

1.0

Vest4

0.12

MutPred

0.41

Loss of MoRF binding (P = 0.0093)

MVP

0.15

MPC

1.4

ClinPred

0.45

GERP RS

4.1

Varity_R

0.21

gMVP

0.17

Mutation Taster

=80/20

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over