7-157416065-G-C

Variant names:

• chr7-157416065-G-C
• NM_058246.4:c.948G>C
• DNAJB6 p.Ser316Ser

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_058246.4(DNAJB6):​c.948G>C​(p.Ser316Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S316S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DNAJB6 NM_058246.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• Publications: 0 publications found

Genes affected

DNAJB6 (HGNC:14888): (DnaJ heat shock protein family (Hsp40) member B6) This gene encodes a member of the DNAJ protein family. DNAJ family members are characterized by a highly conserved amino acid stretch called the 'J-domain' and function as one of the two major classes of molecular chaperones involved in a wide range of cellular events, such as protein folding and oligomeric protein complex assembly. This family member may also play a role in polyglutamine aggregation in specific neurons. Alternative splicing of this gene results in multiple transcript variants; however, not all variants have been fully described. [provided by RefSeq, Jul 2008]

DNAJB6 Gene-Disease associations (from GenCC):

• muscular dystrophy, limb-girdle, autosomal dominant

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=1.65 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058246.4. 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
	DNAJB6	NM_058246.4	MANE Select	c.948G>C	p.Ser316Ser	synonymous	Exon 10 of 10	NP_490647.1	O75190-1
	DNAJB6	NM_001363676.1		c.603G>C	p.Ser201Ser	synonymous	Exon 7 of 7	NP_001350605.1	E9PH18

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAJB6	ENST00000262177.9	TSL:1 MANE Select	c.948G>C	p.Ser316Ser	synonymous	Exon 10 of 10	ENSP00000262177.4	O75190-1
	DNAJB6	ENST00000459889.5	TSL:1	n.*5471G>C		non_coding_transcript_exon	Exon 10 of 10	ENSP00000488263.1	A0A0J9YX62
	DNAJB6	ENST00000459889.5	TSL:1	n.*5471G>C		3_prime_UTR	Exon 10 of 10	ENSP00000488263.1	A0A0J9YX62

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.5
DANN	Benign	0.45
PhyloP100		1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-157208759;