Genetic Variant FAM110D:p.Pro242Arg (chr1-26162016-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024869.3(FAM110D):c.725C>G(p.Pro242Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000727 in 1,237,472 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. 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. P242L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000064 ( 0 hom. )

Consequence

FAM110D
NM_024869.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.247

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06519365).

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.725C>G	p.Pro242Arg	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.725C>G	p.Pro242Arg	missense	Exon 2 of 2	ENSP00000363386.3	Q8TAY7
FAM110D	ENST00000880266.1		c.725C>G	p.Pro242Arg	missense	Exon 3 of 3	ENSP00000550325.1
FAM110D	ENST00000880267.1		c.725C>G	p.Pro242Arg	missense	Exon 3 of 3	ENSP00000550326.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151466

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000645

AC:

AN:

1085898

Hom.:

Cov.:

AF XY:

0.00000775

AC XY:

AN XY:

516136

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22580

American (AMR)

AF:

0.00

AC:

AN:

8134

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13936

East Asian (EAS)

AF:

0.00

AC:

AN:

26080

South Asian (SAS)

AF:

0.00

AC:

AN:

20772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

21322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3230

European-Non Finnish (NFE)

AF:

0.00000648

AC:

AN:

926342

Other (OTH)

AF:

0.0000230

AC:

AN:

43502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

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:

0.0000132

AC:

AN:

151574

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74076

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15208

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67838

Other (OTH)

AF:

0.00

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

0.10

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.0048

Eigen

Benign

-0.63

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.41

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

-0.25

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.74

REVEL

Benign

0.023

Sift

Benign

0.16

Sift4G

Benign

0.071

Polyphen

0.45

Vest4

0.11

MutPred

0.23

Gain of MoRF binding (P = 0.0108)

MVP

0.082

MPC

1.2

ClinPred

0.34

GERP RS

2.3

Varity_R

0.16

gMVP

0.17

Mutation Taster

=98/2

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over