Genetic Variant NM_001395433.1:c.-10G>A (chr16-8884346-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001395433.1(LITAFD):c.-10G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00723 in 399,124 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0068 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0075 ( 8 hom. )

Consequence

LITAFD
NM_001395433.1 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.350

Publications

0 publications found

Variant links:

Genes affected

LITAFD (HGNC:53927): (LITAF domain containing) Predicted to enable metal ion binding activity. Predicted to be located in lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]

LITAFD links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 16-8884346-G-A is Benign according to our data. Variant chr16-8884346-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1675613.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 7 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395433.1. 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
	LITAFD	NM_001395433.1	MANE Select	c.-10G>A		5_prime_UTR	Exon 3 of 4	NP_001382362.1	A0A1B0GVX0
	LITAFD	NM_001395434.1		c.-10G>A		5_prime_UTR	Exon 3 of 4	NP_001382363.1	A0A1B0GVX0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LITAFD	ENST00000636296.2	TSL:5 MANE Select	c.-10G>A	5_prime_UTR	Exon 3 of 4	ENSP00000490685.1	A0A1B0GVX0
LITAFD	ENST00000637237.1	TSL:5	c.-10G>A	5_prime_UTR	Exon 3 of 4	ENSP00000490446.1	A0A1B0GVX0
LITAFD	ENST00000850638.1		c.-10G>A	5_prime_UTR	Exon 4 of 5	ENSP00000520917.1	A0A1B0GVX0

Frequencies

GnomAD3 genomes

AF:

0.00681

AC:

1037

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0270

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00874

Gnomad OTH

AF:

0.00239

GnomAD4 exome

AF:

0.00749

AC:

1849

AN:

246804

Hom.:

Cov.:

AF XY:

0.00738

AC XY:

923

AN XY:

125104

show subpopulations

African (AFR)

AF:

0.00139

AC:

AN:

7182

American (AMR)

AF:

0.00148

AC:

AN:

7430

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9242

East Asian (EAS)

AF:

0.00

AC:

AN:

22892

South Asian (SAS)

AF:

0.000661

AC:

AN:

3028

European-Finnish (FIN)

AF:

0.0242

AC:

515

AN:

21252

Middle Eastern (MID)

AF:

0.000773

AC:

AN:

1294

European-Non Finnish (NFE)

AF:

0.00757

AC:

1197

AN:

158104

Other (OTH)

AF:

0.00690

AC:

113

AN:

16380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

100

201

301

402

502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.00681

AC:

1037

AN:

152320

Hom.:

Cov.:

AF XY:

0.00742

AC XY:

553

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00132

AC:

AN:

41564

American (AMR)

AF:

0.00235

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0270

AC:

287

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00875

AC:

595

AN:

68036

Other (OTH)

AF:

0.00237

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

106

158

211

264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00943

Hom.:

Bravo

AF:

0.00459

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.4

(source)

DANN

Benign

0.69

PhyloP100

-0.35

Splicing

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over