Genetic Variant HSPA12A:c.547-66C>A (chr10-116692533-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_025015.3(HSPA12A):c.547-66C>A variant causes a intron change. The variant allele was found at a frequency of 0.498 in 1,262,098 control chromosomes in the GnomAD database, including 158,194 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.52 ( 21342 hom., cov: 33)

Exomes 𝑓: 0.49 ( 136852 hom. )

Consequence

HSPA12A
NM_025015.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.03

Publications

5 publications found

Variant links:

Genes affected

HSPA12A (HGNC:19022): (heat shock protein family A (Hsp70) member 12A) Predicted to enable ATP binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

HSPA12A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025015.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HSPA12A	NM_025015.3	MANE Select	c.547-66C>A		intron	N/A	NP_079291.2
	HSPA12A	NM_001330164.2		c.598-66C>A		intron	N/A	NP_001317093.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HSPA12A	ENST00000369209.8	TSL:1 MANE Select	c.547-66C>A	intron	N/A	ENSP00000358211.3
HSPA12A	ENST00000674468.1		n.1675C>A	non_coding_transcript_exon	Exon 1 of 2
HSPA12A	ENST00000635765.1	TSL:5	c.598-66C>A	intron	N/A	ENSP00000489674.1

Frequencies

GnomAD3 genomes

AF:

0.525

AC:

79740

AN:

151938

Hom.:

21310

Cov.:

show subpopulations

Gnomad AFR

AF:

0.614

Gnomad AMI

AF:

0.612

Gnomad AMR

AF:

0.473

Gnomad ASJ

AF:

0.597

Gnomad EAS

AF:

0.333

Gnomad SAS

AF:

0.505

Gnomad FIN

AF:

0.512

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.494

Gnomad OTH

AF:

0.541

GnomAD4 exome

AF:

0.494

AC:

548626

AN:

1110040

Hom.:

136852

AF XY:

0.495

AC XY:

279711

AN XY:

564734

show subpopulations

African (AFR)

AF:

0.615

AC:

16541

AN:

26916

American (AMR)

AF:

0.483

AC:

20767

AN:

43010

Ashkenazi Jewish (ASJ)

AF:

0.609

AC:

13494

AN:

22154

East Asian (EAS)

AF:

0.339

AC:

12843

AN:

37872

South Asian (SAS)

AF:

0.515

AC:

38221

AN:

74250

European-Finnish (FIN)

AF:

0.514

AC:

26105

AN:

50766

Middle Eastern (MID)

AF:

0.596

AC:

2994

AN:

5024

European-Non Finnish (NFE)

AF:

0.490

AC:

392740

AN:

801314

Other (OTH)

AF:

0.511

AC:

24921

AN:

48734

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

14052

28104

42156

56208

70260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10062

20124

30186

40248

50310

<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:

0.525

AC:

79815

AN:

152058

Hom.:

21342

Cov.:

AF XY:

0.525

AC XY:

39014

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.615

AC:

25482

AN:

41458

American (AMR)

AF:

0.473

AC:

7222

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.597

AC:

2074

AN:

3472

East Asian (EAS)

AF:

0.333

AC:

1716

AN:

5156

South Asian (SAS)

AF:

0.502

AC:

2420

AN:

4822

European-Finnish (FIN)

AF:

0.512

AC:

5413

AN:

10576

Middle Eastern (MID)

AF:

0.653

AC:

192

AN:

294

European-Non Finnish (NFE)

AF:

0.494

AC:

33589

AN:

67970

Other (OTH)

AF:

0.544

AC:

1149

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1985

3970

5954

7939

9924

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

706

1412

2118

2824

3530

<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:

0.523

Hom.:

2722

Bravo

AF:

0.526

Asia WGS

AF:

0.463

AC:

1611

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

9.4

(source)

DANN

Benign

0.68

PhyloP100

4.0

PromoterAI

-0.0090

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over